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一组暴露于战争环境危害的伊拉克患者膀胱移行细胞癌中p53基因的特定突变模式

Specific-mutational patterns of p53 gene in bladder transitional cell carcinoma among a group of Iraqi patients exposed to war environmental hazards.

作者信息

Al-Kashwan Thekra A, Houshmand Massoud, Al-Janabi Asaad, Melconian Alice K, Al-Abbasi Dhafir, Al-Musawi Muhammad N, Rostami Maryam, Yasseen Akeel A

机构信息

Middle Euphrates unit for cancer research, Faculty of Medicine, University of Kufa, Kufa, Iraq.

出版信息

BMC Res Notes. 2012 Aug 28;5:466. doi: 10.1186/1756-0500-5-466.

Abstract

BACKGROUND

To unfold specific-mutational patterns in TP53 gene due to exposures to war environmental hazards and to detect the association of TP53 gene alteration with the depth of bladder cancer.

METHODS

Twenty-nine bladder carcinomas were analyzed for TP53 alterations. PCR-single strand conformational polymorphism analysis, DNA sequencing and immunohistochemical analysis using monoclonal mouse anti-human p53 antibody (Clone DO-7) were employed.

RESULTS

TP53 gene mutations occurred in 37.9% of the cases while TP53 overexpression occurred in 58.6%. Both of them were associated with deep invasive-tumors. Single mutations were seen in 63.6%, whereas only 27.3% have shown double mutations. Four mutations were frameshifted (30.8%); two of them showed insertion A after codon 244. There was no significant association between TP53 mutations and protein overexpression (P>0.05), while a significant association was observed between TP53 alterations and tumors progression (P ≤ 0.01).

CONCLUSION

The infrequent TP53mutations, especially insertion A and 196 hotspot codon, may represent the specific-mutational patterns in bladder carcinoma among the Iraqi patients who were exposed to war environmental hazards. TP53 alteration associated with bladder cancer progression should be analyzed by both mutational and protein expression analysis.

摘要

背景

揭示因暴露于战争环境危害而导致的TP53基因特定突变模式,并检测TP53基因改变与膀胱癌深度的关联。

方法

对29例膀胱癌进行TP53改变分析。采用聚合酶链反应-单链构象多态性分析、DNA测序以及使用小鼠抗人p53单克隆抗体(克隆号DO-7)进行免疫组织化学分析。

结果

37.9%的病例发生TP53基因突变,58.6%的病例出现TP53过表达。两者均与深层浸润性肿瘤相关。63.6%的病例出现单突变,而仅有27.3%表现为双突变。4个突变是移码突变(30.8%);其中2个在密码子244后出现插入A。TP53突变与蛋白过表达之间无显著关联(P>0.05),而TP53改变与肿瘤进展之间存在显著关联(P≤0.01)。

结论

罕见的TP53突变,尤其是插入A和196热点密码子,可能代表了暴露于战争环境危害的伊拉克患者膀胱癌中的特定突变模式。应通过突变分析和蛋白表达分析来分析与膀胱癌进展相关的TP53改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc1e/3439300/38c8f1bec861/1756-0500-5-466-1.jpg

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